The primary objective of the Center for Research on Environmental Disease (CRED) for the next 5 year funding period is to study the mechanisms by which environmental factors may cause or influence human disease and to develop methods for early detection, prevention and control of environmentally related diseases. The theme for the CRED over the next funding period is to define molecular responses to environmental exposures and to understand the genetic basis for variability in these responses. Because the problems of environmental health are complex, requiring an understanding of the sources of chemical and physical stresses in the environment, their modes of transport and transformation, the routes of human exposure, the mechanisms through which the agents exert their effects, and the possible ways their actions may be influenced by modifiers or co-factors, including genetic background, the successful study of these complex problems requires interdisciplinary approaches. To teach this vast array of problems, the CRED brings together , in an integrated effort, a multi-disciplinary group of established scientists with an extremely broad range of an integrated effort, a multi-disciplinary group of established scientists with an extremely broad range of expertise. In addition, the CRED will continue to provide these investigators access to sophisticated biochemical molecular, and analytical techniques to enhance research efforts that revolve around the theme. This Center consists of five Research Cores: i) Mechanisms of Toxicity and Cell Death; ii) Cellular Responses to DNA Damage; iii) Molecular Genetics and Environmental Carcinogenesis and Environmental Carcinogenesis; iv) Molecular Epidemiology and Ecogenetics; and vi) Mechanisms of Disease Prevention. The research efforts of these Research Cores will be enhanced by access to the following seven Facility Cores: i) Molecular Biology; ii) Transgenic Animals; iii) Histology and Tissue Processing; iv) Functional Genomics. In addition, an Administrative Core formalizes collaborative interactions and provides for Enrichment Activities as well as a Pilot Project Program. Finally, a Community Outreach and Education Program also establishes a mechanism to disseminate important research findings of the Center to the general community, as well as provides community education programs with an emphasis on issues related to environmental health sciences.